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Myeloid derived suppressor cells

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https://www.readbyqxmd.com/read/29150986/memory-t-cells-are-significantly-increased-in-rejecting-liver-allografts-of-rhesus-monkeys
#1
Hwajung Kim, Hyeyoung Kim, Sun-Kyung Lee, Xue-Li Jin, Tae Jin Kim, Chanho Park, Jae-Il Lee, Hyo-Sin Kim, Suk Kyun Hong, Kyung Chul Yoon, Sung Woo Ahn, Kyoung-Bun Lee, Nam-Joon Yi, Jaeseok Yang, Kwang-Woong Lee, Wayne J Hawthorne, Kyung-Suk Suh
INTRODUCTION: The Rhesus monkey (RM) is an excellent preclinical model in kidney, heart and islet transplantation that has provided the basis for new immunosuppressive protocols for clinical studies. However, there remain relatively few liver transplantation (LT) models in nonhuman primates. In this study, we analyzed the immune cell populations of PBMCs and secondary lymphoid organs along with livers of normal rhesus monkeys and compared them to those of rejecting liver transplanted recipient's following withdrawal of immunosuppression...
November 18, 2017: Liver Transplantation
https://www.readbyqxmd.com/read/29147615/tumor-associated-neutrophils-induce-apoptosis-of-non-activated-cd8-t-cells-in-a-tnf%C3%AE-and-no-dependent-mechanism-promoting-a-tumor-supportive-environment
#2
Janna Michaeli, Merav E Shaul, Inbal Mishalian, Avi-Hai Hovav, Liran Levy, Lidia Zolotriov, Zvi Granot, Zvi G Fridlender
The role of neutrophils in tumor progression has become in recent years a subject of growing interest. Tumor-associated neutrophils (TANs), which constitute an important portion of the tumor microenvironment, promote immunosuppression in advanced tumors by modulating the proliferation, activation and recruitment of a variety of immune cell types. Studies which investigated the consequences of manipulating TAN polarization suggest that the impact of these neutrophils on tumor progression is considerably mediated by and dependent on the presence of CD8 T-cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29143813/ship1-but-not-an-aml-derived-ship1-mutant-suppresses-myeloid-leukemia-growth-in-a-xenotransplantation-mouse-model
#3
M Täger, S Horn, E Latuske, P Ehm, M Schaks, M Nalaskowski, B Fehse, W Fiedler, C Stocking, J Wellbrock, M Jücker
Constitutive activation of the PI3K/AKT signaling pathway is found in ~50-70% of AML patients. The SH2-containing inositol 5-phosphatase 1 (SHIP1) is a negative regulator of PI3K/AKT signaling in hematopoietic cells. SHIP1 knockout mice develop a myeloproliferative syndrome and concomitant deletion of SHIP1 and the tumor suppressor PTEN leads to the development of lethal B-cell lymphomas. In the study presented here, we investigated the role of SHIP1 as a tumor suppressor in myeloid leukemia cells in an in vivo xenograft transplantation model...
November 16, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29142311/a-standardized-herbal-extract-mitigates-tumor-inflammation-and-augments-chemotherapy-effect-of-docetaxel-in-prostate-cancer
#4
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Yu-Chih Yang, Yi-Wen Hsiao, Mong-Hsun Tsai, Pei-Wen Hsiao
Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141759/cell-type-specific-immunomodulation-induced-by-helminthes-effect-on-metainflammation-insulin-resistance-and-type-2-diabetes
#5
Vivekanandhan Aravindhan, Gowrishankar Anand
Recent epidemiological studies have documented an inverse relationship between the decreasing prevalence of helminth infections and the increasing prevalence of metabolic diseases ("metabolic hygiene hypothesis"). Chronic inflammation leading to insulin resistance (IR) has now been identified as a major etiological factor for a variety of metabolic diseases other than obesity and Type-2 diabetes (metainflammation). One way by which helminth infections such as filariasis can modulate IR is by inducing a chronic, nonspecific, low-grade, immune suppression mediated by modified T-helper 2 (Th2) response (induction of both Th2 and regulatory T cells) which can in turn suppress the proinflammatory responses and promote insulin sensitivity (IS)...
October 30, 2017: American Journal of Tropical Medicine and Hygiene
https://www.readbyqxmd.com/read/29139571/human-prosthetic-joint-infections-are-associated-with-myeloid-derived-suppressor-cells-mdscs-implications-for-infection-persistence
#6
Cortney E Heim, Debbie Vidlak, Jessica Odvody, Curtis W Hartman, Kevin L Garvin, Tammy Kielian
Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33(+) HLA-DR(-) CD66b(+) CD14(-/low) granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues...
November 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/29139296/differential-content-of-proteins-mrnas-and-mirnas-suggests-that-mdsc-and-their-exosomes-may-mediate-distinct-immune-suppressive-functions
#7
Lucia Geis-Asteggiante, Ashton T Belew, Virginia K Clements, Nathan J Edwards, Suzanne Ostrand-Rosenberg, Nagib M El-Sayed, Catherine Fenselau
Myeloid-derived suppressor cells (MDSC) are immature myeloid cells that accumulate in the circulation and the tumor microenvironment of most cancer patients. There, MDSC suppress both adaptive and innate immunity, hindering immunotherapies. The inflammatory milieu often present in cancers facilitates MDSC suppressive activity, causing aggressive tumor progression and metastasis. MDSC from tumor-bearing mice release exosomes, which carry biologically active proteins and mediate some of the immunosuppressive functions characteristic of MDSC...
November 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/29137411/a-novel-polyamine-blockade-therapy-activates-an-anti-tumor-immune-response
#8
Eric T Alexander, Allyson Minton, Molly C Peters, Otto Phanstiel, Susan K Gilmour
Most tumors maintain elevated levels of polyamines to support their growth and survival. This study explores the anti-tumor effect of polyamine starvation via both inhibiting polyamine biosynthesis and blocking the upregulated import of polyamines into the tumor. We demonstrate that polyamine blockade therapy (PBT) co-treatment with both DFMO and a novel polyamine transport inhibitor, Trimer PTI, significantly inhibits tumor growth more than treatment with DFMO or the Trimer PTI alone. The anti-tumor effect of PBT was lost in mice where CD4(+) and CD8(+) T cells were antibody depleted, implying that PBT stimulates an anti-tumor immune effect that is T-cell dependent...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137229/activation-of-vip-signaling-enhances-immunosuppressive-effect-of-mdscs-on-cmv-induced-adaptive-immunity
#9
Parvin Forghani, Christopher T Petersen, Edmund K Waller
Vasoactive intestinal peptide (VIP) is recognized as a potent anti-inflammatory factor which affects both the innate and adaptive arms of the immune system. These effects include, but are not limited to, inhibition of T cell proliferation and disruption of immune homeostasis. Myeloid-derived suppressor cells (MDSC) are an immune regulatory cell type that has been described in settings of cancer and infectious disease._Here we demonstrate a reduced circulating monocytic MDSCs in the VIP (-/-)vs. wild type MCMV...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136520/characterization-of-myeloid-cell-populations-in-human-testes-collected-after-sex-reassignment-surgery
#10
Rosalie Ponte, Franck P Dupuy, Fadi Brimo, Vikram Mehraj, Pierre Brassard, Maud Belanger, Ekaterina Yurchenko, Mohammad-Ali Jenabian, Nicole F Bernard, Jean-Pierre Routy
The testis has been described in animal models as a site of immune privilege, which protects spermatids against tissue damage during inflammation. Myeloid cells, including macrophages and dendritic cells (DC), are defined as key players in the testicular immune privilege in animal models. However, their distribution and frequency in human testis remain poorly described. To overcome the challenges related to tissue sampling, we obtained testicular tissue from men under hormonal therapy who elected to have sex reassignment surgery (SRS)...
October 14, 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/29133913/nitric-oxide-mediated-inhibition-of-antigen-presentation-from-dcs-to-cd4-t-cells-in-cancer-and-measurement-of-stat1-nitration
#11
Joseph Markowitz, Jiang Wang, Zach Vangundy, Jia You, Vedat Yildiz, Lianbo Yu, Isaac P Foote, Owen E Branson, Andrew R Stiff, Taylor R Brooks, Brandon Biesiadecki, Thomas Olencki, Susheela Tridandapani, Michael A Freitas, Tracey Papenfuss, Mitch A Phelps, William E Carson
Myeloid derived suppressor cells (MDSC) produce nitric oxide (NO) and inhibit dendritic cell (DC) immune responses in cancer. DCs present cancer cell antigens to CD4(+) T cells through Jak-STAT signal transduction. In this study, NO donors (SNAP and DETA-NONOate) inhibited DC antigen presentation. As expected, MDSC isolated from peripheral blood mononuclear cells (PBMC) from cancer patients produced high NO levels. We hypothesized that NO producing MDSC in tumor-bearing hosts would inhibit DC antigen presentation...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29133357/myeloid-derived-suppressor-cells-ameliorate-cyclosporine-a-induced-hypertension-in-mice
#12
Valorie L Chiasson, Kelsey R Bounds, Piyali Chatterjee, Lochana Manandhar, Abhinandan R Pakanati, Marcos Hernandez, Bilal Aziz, Brett M Mitchell
The calcineurin inhibitor cyclosporine A (CsA) suppresses the immune system but promotes hypertension, vascular dysfunction, and renal damage. CsA decreases regulatory T cells and this contributes to the development of hypertension. However, CsA's effects on another important regulatory immune cell subset, myeloid-derived suppressor cells (MDSCs), is unknown. We hypothesized that augmenting MDSCs would ameliorate the CsA-induced hypertension and vascular and renal injury and dysfunction and that CsA reduces MDSCs in mice...
November 13, 2017: Hypertension
https://www.readbyqxmd.com/read/29132870/mtor-inhibitor-rapamycin-induce-polymorphonuclear-myeloid-derived-suppressor-cells-mobilization-and-function-in-protecting-against-acute-graft-versus-host-disease-after-bone-marrow-transplantation
#13
Yu Lin, Binsheng Wang, Wei Shan, Yamin Tan, Jingjing Feng, Lin Xu, Limengmeng Wang, Biqing Han, Mingming Zhang, Jian Yu, Xiaohong Yu, He Huang
The mammalian target of rapamycin (mTOR) inhibitor rapamycin (RAPA) has been shown to be an effective immunosuppressor in the management of acute graft-versus-host disease (aGVHD) after bone marrow transplantation. Myeloid-derived suppressor cells (MDSCs) also have a protective effect in aGVHD regulation. However, the relationship between RAPA and MDSCs in aGVHD models is unclear. Meanwhile, the effect of RAPA on different subgroups of MDSCs is also less well described. In this study, we demonstrate that in vivo administration of RAPA results in the expansion and functional enhancement of polymorphonuclear MDSCs (PMN-MDSCs) in a murine model of aGVHD...
November 10, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/29130057/differentiation-of-myeloid-derived-suppressor-cells-from-murine-bone-marrow-and-their-co-culture-with-splenic-dendritic-cells
#14
Giada Mondanelli, Claudia Volpi
Myeloid-derived suppressor cells (MDSCs) possess the ability to suppress the immune response, and to amplify the regulatory properties of other immune cells, i.e., dendritic cells. Here we describe a protocol in which MDSCs were differentiated from murine bone marrow cells, and CD11c(+) dendritic cells were purified from murine spleens. MDSCs and CD11c dendritic cells can be co-cultured and the immunoregulatory phenotype of the MDSCs-conditioned dendritic cells could be assessed by means of a specific functional in vivo experiment, i...
September 20, 2017: Bio-protocol
https://www.readbyqxmd.com/read/29129292/targeting-myeloid-cells-in-the-tumor-sustaining-microenvironment
#15
REVIEW
Jonathan Schupp, Franziska K Krebs, Niklas Zimmer, Emily Trzeciak, Detlef Schuppan, Andrea Tuettenberg
Myeloid cells are the most abundant cells in the tumor microenvironment (TME). The tumor recruits and modulates endogenous myeloid cells to tumor-associated macrophages (TAM), dendritic cells (DC), myeloid-derived suppressor cells (MDSC) and neutrophils (TAN), to sustain an immunosuppressive environment. Pathologically overexpressed mediators produced by cancer cells like granulocyte-macrophage colony-stimulating- and vascular endothelial growth factor induce myelopoiesis in the bone marrow. Excess of myeloid cells in the blood, periphery and tumor has been associated with tumor burden...
November 2, 2017: Cellular Immunology
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#16
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29124314/prophylactic-dna-vaccine-targeting-foxp3-regulatory-t-cells-depletes-myeloid-derived-suppressor-cells-and-improves-anti-melanoma-immune-responses-in-a-murine-model
#17
Afshin Namdar, Reza Mirzaei, Arash Memarnejadian, Roobina Boghosian, Morteza Samadi, Hamid Reza Mirzaei, Hamid Farajifard, Mehdi Zavar, Kayhan Azadmanesh, Shokrollah Elahi, Farshid Noorbakhsh, Abbas Rezaei, Jamshid Hadjati
Regulatory T cells (Treg) and myeloid-derived suppressor cells (MDSC) are the two important and interactive immunosuppressive components of the tumor microenvironment that hamper anti-tumor immune responses. Therefore, targeting these two populations together might be beneficial for overcoming immune suppression in the tumor microenvironment. We have recently shown that prophylactic Foxp3 DNA/recombinant protein vaccine (Foxp3 vaccine) promotes immunity against Treg in tumor-free conditions. In the present study, we investigated the immune modulatory effects of a prophylactic regimen of the redesigned Foxp3 vaccine in the B16F10 melanoma model...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29123954/exogenous-lipid-uptake-induces-metabolic-and-functional-reprogramming-of-tumor-associated-myeloid-derived-suppressor-cells
#18
Amir A Al-Khami, Liqin Zheng, Luis Del Valle, Fokhrul Hossain, Dorota Wyczechowska, Jovanny Zabaleta, Maria D Sanchez, Matthew J Dean, Paulo C Rodriguez, Augusto C Ochoa
Myeloid-derived suppressor cells (MDSC) promote tumor growth by blocking anti-tumor T cell responses. Recent reports show that MDSC increase fatty acid uptake and fatty acid oxidation (FAO) to support their immunosuppressive functions. Inhibition of FAO promoted a therapeutic T cell-mediated anti-tumor effect. Here, we sought to determine the mechanisms by which tumor-infiltrating MDSC increase the uptake of exogenous lipids and undergo metabolic and functional reprogramming to become highly immunosuppressive cells...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/29123081/resistance-to-cancer-immunotherapy-mediated-by-apoptosis-of-tumor-infiltrating-lymphocytes
#19
Jingjing Zhu, Céline G Powis de Tenbossche, Stefania Cané, Didier Colau, Nicolas van Baren, Christophe Lurquin, Anne-Marie Schmitt-Verhulst, Peter Liljeström, Catherine Uyttenhove, Benoit J Van den Eynde
Despite impressive clinical success, cancer immunotherapy based on immune checkpoint blockade remains ineffective in many patients due to tumoral resistance. Here we use the autochthonous TiRP melanoma model, which recapitulates the tumoral resistance signature observed in human melanomas. TiRP tumors resist immunotherapy based on checkpoint blockade, cancer vaccines or adoptive T-cell therapy. TiRP tumors recruit and activate tumor-specific CD8(+) T cells, but these cells then undergo apoptosis. This does not occur with isogenic transplanted tumors, which are rejected after adoptive T-cell therapy...
November 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/29120053/tumor-conditions-induce-bone-marrow-expansion-of-granulocytic-but-not-monocytic-immunosuppressive-leukocytes-with-increased-cxcr2-expression-in-mice
#20
Zhen Bian, Lei Shi, Mahathi Venkataramani, Ahmed Mansour Abdelaal, Courtney Culpepper, Koby Kidder, Hongwei Liang, Ke Zen, Yuan Liu
Myeloid-derived suppressor cells (MDSCs) promote tumor growth through, in part, inhibiting T cell immunity. However, mechanisms underlying MDSC expansion and guidance of MDSCs toward the tumor microenvironment remain unclear. Employing Percoll density gradients, we separate bone marrow (BM) leukocytes from tumor-bearing mice into four density-increasing bands with myeloid leukocytes enriched in bands III and IV. Band III comprises monocytes and low-density granulocytes, both confirmed to be M-MDSCs and G-MDSCs, respectively, by displaying potent inhibition of T cell proliferation...
November 9, 2017: European Journal of Immunology
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